Extinction of fear, the process by which conditioned fear is no longer evoked in response to a conditioned stimulus, has received considerable experimental investigation in both rodents and humans. However, the return of fear after extinction, termed renewal, has received less experimental analysis, particularly in human subjects. Fear renewal is a major public health concern because it occurs after extinction therapy in populations with PTSD and other anxiety related disorders. Evidence in rodents suggests that after extinction contextual cues regulate the renewal of fear and this process is hippocampus-dependent. The specific aims of this proposal will (1) demonstrate fear renewal in human subjects in a clinically relevant and hippocampus- dependent paradigm in the laboratory, (2) investigate how contextual cues regulate the renewal of conditioned fear using virtual reality contexts, (3) implement virtual contexts within an fMRI scanner to investigate the pattern of brain activation during fear renewal. The proposed studies will contribute to understanding basic mechanisms that support fear renewal. Moreover, the findings will provide a direct link between evidence from rodent studies and application for a clinical setting. [unreadable] [unreadable] [unreadable]